title: Isorhamnetin represses adipogenesis in 3T3-L1 cells.
abstract: Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP-beta and -delta, the upstream regulators of PPAR-gamma and C/EBP-alpha, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR-gamma target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor-alpha (LXR-alpha) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR-gamma expression as a possible mechanism underlying the isorhamnetin-mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR-gamma and C/EBP-alpha.
authors.affiliation: Biospectrum Life Science Institute, Gunpo City, Gyunggi Do, Republic of Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Jienny
authors.initials: J
authors.lastname: Lee
authors.forename: Saebom
authors.initials: S
authors.lastname: Kim
authors.forename: Sungran
authors.initials: S
authors.lastname: Huh
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Yongwoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang Yo
authors.initials: SY
authors.lastname: Byun
authors.forename: Yeong-Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D044948:Flavonols / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D051767:Early Growth Response Protein 2; D044948:Flavonols; D047495:PPAR gamma; D012333:RNA, Messenger; D014157:Transcription Factors; D014280:Triglycerides; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; C047368:3-methylquercetin; D011794:Quercetin; D005993:Glycerolphosphate Dehydrogenase